Despite the advances in diagnosis and treatment of infectious disease, meningitis is still an important cause of morbidity and mortality. Early diagnosis and effective therapy are the key factors to reduce the morbidity and mortality associated with meningitis. The routine clinical criteria, gram staining, WBC and neutrophil count, or CSF (Protein level, glucose level, WBC count or neutrophil count) 79-82 used alone are not sensitive and specific for distinguishing bacteria and aseptic meningitis; it also takes a longer turn-around time.
Different studies have shown elevated PCT level exclusively in patients with bacterial meningitis while low levels were found in viral/aseptic meningitis.5,6
Procalcitonin is not produced in CSF and is always low in CSF even in bacterial meningitis.83 Elevated procalcitonin levels have also been seen in meningococcal infections.
Meningococcal infection is associated with high mortality risk. Elevated Procalcitonin values (> 10ng/ml) indicate a high risk of death and a high risk for organ dysfunction.84,85 In a study, 94 children with confirmed meningococcal disease, Procalcitonin was shown to be a more sensitive and specific predictor of meningococcal disease in children with fever and rash.86
22 Procalcitonin has been used to determine duration of therapy. Daily Procalcitonin level measurement permitted significant reduction in the quantity of antibiotics used and the duration of care during a meningitis epidemic in France compared to an early epidemic (from 46% to 29% and 4.5 to 2.1 days) 46%.87
2.9.4.2 Diagnostic use of Procalcitonin in viral infections
Procalcitonin level remains low during viral infections. It is induced only in small amounts.
In a prospective study conducted in a pediatric emergency department, 240 children with viral infection, 5% had PCT >1ng/ml, 0.8% had PCT >2ng/ml. The highest level recorded did not exceed 5ng/ml and it was found in a patient with macrophage activation disorder in which pro-inflammatory cytokines are produced.88 In a study of Epstein Barr Virus infection, 23 of 25 children had PCT values of under 0.5ng/ml.89 In a study involving children with disease of the airways and Respiratory syncytial virus positive bronchiolitis, PCT value in the children was less than 0.5ng/ml.90
2.9.4.3 Diagnostic use of Procalcitonin in bacteremia
Procalcitonin levels are higher in patients with positive blood cultures than in patients with the same disease without positive blood culture. Procalcitonin is elevated when there is evidence of bacterial agents in blood.91 In a study, procalcitonin was used to differentiate bloodstream infection from contamination with Coagulase negative Staphylococcus species, procalcitonin levels were significantly lower in patients with contamination than in bacteremic patients.92
Numerous studies have shown that low procalcitonin levels have a high negative predictive value for the exclusion of bacteraemia.93,94 High procalcitonin levels are usually seen in
23 patients with positive blood culture and positive blood cultures are frequently seen in patients with high PCT levels or severe sepsis and those with organ dysfunctions.
2.9.4.4 Diagnostic use of Procalcitonin in sepsis
The use of appropriate antimicrobial therapy for sepsis more often than not depends on the incriminating pathogens. The clinical manifestations of sepsis due to either gram positive or gram negative bacteria are the same making the choice of antibiotics difficult till result of blood culture is available. Procalcitonin levels have been shown to be higher in bacteremic but lower in non-bacteremic conditions.91 Studies have shown that procalcitonin levels can be used to differentiate gram negative sepsis from gram positive sepsis.95 Procalcitonin levels have been found to be significantly elevated in gram negative sepsis and lower in gram positive & fungal sepsis.96
2.9.4.5 Diagnostic use of Procalcitonin in Pneumonia
Pneumonia and other lower respiratory tract infections are among the leading causes of death worldwide. Pneumonia is associated with significant morbidity and mortality, proper diagnosis and management of patients are important. Pneumonia can be classified into different forms. It can be classified into different types depending on the cause and type of agent. It can be community acquired pneumonia (CAP) or hospital acquired pneumonia (HAP). It can also be classified by the type of agents, e.g. atypical agents, fungal, viral or tuberculosis.
The diagnosis of pneumonia is primarily a clinical diagnosis. It can be based on 1. Suspicion of an infection of the airways
2. Indication of involvement of the lung parenchyma from a chest X-ray.
24 3. Signs of inflammation e.g. fever, elevated inflammatory marker, leukocytosis.
Type of agent, severity of pneumonia and degree of systemic inflammatory response have been shown to be inducers of PCT. Numerous studies have shown different levels of measured Procalcitonin in pneumonia.97-103 Procalcitonin has been shown to be related to the mortality risk of disease. Very low Procalcitonin values characterized patients with low mortality in CAP.104,105 Elevated Procalcitonin levels have been observed in bacteria and Legionella pneumonia, while low levels have been seen in viral pneumonia or pneumonia due to atypical organisms such as chlamydia or mycoplasmas.98,99,105,106 Several studies have reported only slightly elevated PCT levels of 0.3ng/ml to around 1ng/ml in active pulmonary tuberculosis.107-108 Also, Procalcitonin concentration in patients with pleural effusion associated with tuberculosis has been in the low range (0.1-0.3ng/ml).109
Procalcitonin has been used to significantly reduce duration of therapy in patients with pneumonia or sepsis.12,14 Different studies have shown decreasing level of Procalcitonin in patients with ventilator associated pneumonia as an indication of a good prognosis and as well as effectiveness of therapy.9,97,100,101 Monitoring of Procalcitonin levels have been used to reduce the duration of antibiotics treatment in patients with ventilator-associated pneumonia and also to distinguish those responding to treatment from those who are not responding.112,113
In summary, elevated PCT level indicates a higher probability of the presence of bacterial pneumonia. Low PCT level occurs more often in less severe pneumonia or those with low mortality risk to the patient, or viral or atypical pneumonia. Procalcitonin can also be used to determine whether antibiotic treatment is necessary or not. It can also provide information about the success of therapy as well as the prognosis for the disease.
25 2.9.4.6 Diagnostic use of Procalcitonin in bacterial endocarditis
Despite not being the gold standard in diagnosis of endocarditis, elevated procalcitonin levels have been seen in patients with endocarditis. It has been shown to be highly sensitive and specific in diagnosing endocarditis.114 High serum PCT levels has been reported in those with infective endocarditis compared with those with other diagnosis.115
2.9.4.7 Diagnostic use of Procalcitonin in gastroenteritis
Gastroenteritis, a leading cause of death among under five years of age. It can be due to both infectious and non-infectious causes. Many microbial pathogens have been identified.
Procalcitonin was found to be a good diagnostic marker of bacterial gastroenteritis.116 Also in study of diarrhoea with various etiologies, procalcitonin was found to be lower in children with viral gastroenteritis.117